Germinal centers (GCs) are the site of maturation of antibody affinity and are thus of key importance to humoral immunity. The study of B-cell dynamics and selection within the GC has been hampered by the limited number of techniques available to manipulate GC output in vivo. Here, we describe an approach to trigger positive selection of B cells in vivo by targeting antigen specifically to a subpopulation of GC B cells via the surface lectin DEC-205 and forcing their interaction with T follicular helper cells. Targeted GC B cells can then be followed over time as they progress through the stages of positive selection.